Natural product compositions for treating or managing symptoms of add, adhd, anxiety, and depression

ABSTRACT

Disclosed herein are natural product compositions for treating ADHD and related disorders.

CROSS REFERENCE TO RELATED APPLICATIONS

The present disclosure is a continuation-in-part of U.S. applicationSer. No. 16/806,704 filed on Feb. 12, 2020, which is a continuation ofU.S. application Ser. No. 15/985,610 filed on May 21, 2018, whichapplication claims priority to and the benefit of the filing date ofU.S. Provisional Application No. 62/589,916, filed Nov. 22, 2017 andwhich also claims priority to and the benefit of the filing date of U.S.Provisional Application No. 62/510,156, filed May 23, 2017, thedisclosures of each are hereby incorporated by reference herein in theirentireties.

BACKGROUND OF THE DISCLOSURE

Attention deficit disorder/attention deficit hyperactivity disorder(ADD/ADHD) and related disorders are common in children, adolescents andadults. The recent increase in the number of cases of attention deficithyperactivity disorder (ADHD) and related disorders has been accompaniedby a surge in the use of prescription psychopharmacological treatments.Stimulants such as methylphenidate (Ritalin) and amphetamines are themost common type of medication used for treating ADHD. These medicationscan activate brain circuits that support attention and focused behavior.Ritalin is a class 2 narcotic, with risk of abuse. Other non-stimulantmedications, such as atomoxetine, guanfacine, and clonidine, are alsoavailable. For many children, ADHD medications reduce hyperactivity andimpulsivity and improve their ability to focus, work, and learn.Children taking medications, however, must be monitored closely andcarefully for compliancy, and for the commonly reported side-effectssuch as decreased appetite, sleep problems, anxiety and irritability.Some children report mild stomach aches or headaches. Other, lessfrequent side effects include cardiovascular or psychiatric problems.

Adults with ADHD are treated with medication, psychotherapy, or acombination of treatments. Adult prescriptions for stimulants and othermedications, however, require special considerations, including the needto avoid dangerous drug interactions with commonly used medications forphysical problems such as diabetes, high blood pressure, highcholesterol, anxiety and depression etc.

There remains a need for a safe and effective treatment for adult andpediatric ADHD and related disorders.

BRIEF SUMMARY OF THE DISCLOSURE

In one aspect of the present disclosure is a formulation which includesnatural ingredients, and which are useful in treating a subject havingADD/ADHD or a related disorder, or one or more symptoms of ADD/ADHD. Inanother aspect of the present disclosure is a formulation which includesnatural ingredients, and which are useful in reducing symptoms ADD/ADHDor a related disorder, or one or more symptoms of ADD/ADHD. In anotheraspect of the present disclosure is a formulation which includes naturalingredients, and which are useful in managing or controlling symptoms ofADD/ADHD or a related disorder, or one or more symptoms of ADD/ADHD.

In another aspect of the present disclosure is a formulation whichincludes natural ingredients, and which are useful in treating a subjecthaving anxiety. In another aspect of the present disclosure is aformulation which includes natural ingredients, and which are useful inreducing symptoms of anxiety. In another aspect of the presentdisclosure is a formulation which includes natural ingredients, andwhich are useful in managing or controlling symptoms of anxiety.

In another aspect of the present disclosure is a formulation whichincludes natural ingredients, and which are useful in treating a subjecthaving depression. In another aspect of the present disclosure is aformulation which includes natural ingredients, and which are useful inreducing symptoms of depression. In another aspect of the presentdisclosure is a formulation which includes natural ingredients, andwhich are useful in managing or controlling symptoms of depression.

In one aspect of the present disclosure is a natural product compositioncomprising (i) at least three natural products selected from the groupconsisting of cannabidiol, spikenard, a root extract from a Valerianspecies, passion flower extract, and ashwagandha, and (ii) apharmaceutically acceptable carrier or excipient. In some embodiments,the natural product composition is free from caffeine or other likestimulants. In some embodiments, the natural product composition is freefrom theanine.

In some embodiments, the natural product composition comprises at leastcannabidiol, spikenard, and a root extract from a Valerian species. Insome embodiments, the natural product composition comprises at leastfour of a cannabidiol, spikenard, valerian root, passion flow extract,and ashwagandha. In some embodiments, the natural product compositioncomprises at least a cannabidiol, spikenard, a root extract from aValerian species, and ashwagandha.

In another aspect of the present disclosure is a multi-componentcomposition including cannabidiol, spikenard, valerian root, passionflow extract, and ashwagandha. In some embodiments, the multi-componentcomposition is mixed with a pharmaceutically acceptable carrier orexcipient to provide a pharmaceutical formulation. In some embodiments,the pharmaceutical formulation comprises from between about 1% to about99% by total weight of a carrier or excipient, e.g. water.

In another aspect of the present disclosure is a natural productcomposition comprising (i) passion flower in an amount ranging frombetween about 5% to about 17.5% by total weight of the natural productcomposition; (ii) a root extract from a Valerian species in an amountranging from between about 30% to about 60% by total weight of thenatural product composition; (iii) Ashwagandha in an amount ranging frombetween about 10% to about 30% by total weight of the natural productcomposition; (iv) spikenard in an amount ranging from between about 5%to about 20% by total weight of the natural product composition; and (v)cannabidiol in an amount ranging from between about 2% to about 20% bytotal weight of the natural product composition. In some embodiments,the natural product composition may be admixed with a pharmaceuticallyacceptable excipient or carrier to provide a suitable formulation foradministration to a patient in need thereof. In some embodiments, aratio of an amount of a natural product composition to an amount of apharmaceutically acceptable excipient or carrier ranges from about 10:1to about 1:10. In some embodiments, the ratio ranges from about 5:1 toabout 1:5.

In another aspect of the present disclosure is a method of treating ADHDcomprising administering to a subject in need thereof a formulationcomprising a comprising (i) a cannabidiol, spikenard, valerian root,passion flow extract, and ashwagandha; and (ii) a pharmaceuticallyacceptable carrier or excipient. In some embodiments, the administrationof the formulation does not cause a substantial increase in serotoninlevels.

In another aspect of the present disclosure is a method of reducing orameliorating the symptoms of ADD, ADHD, or related disorders comprisingadministering to a subject in need thereof a natural product compositioncomprising (i) a cannabidiol, spikenard, valerian root, passion flowextract, and ashwagandha; and (ii) a pharmaceutically acceptable carrieror excipient. In some embodiments, the administration of the naturalproduct composition does not cause a substantial increase in serotoninlevels.

In another aspect of the present disclosure is a method of treatinganxiety comprising administering to a subject in need thereof aformulation comprising a comprising (i) a cannabidiol, spikenard,valerian root, passion flow extract, and ashwagandha; and (ii) apharmaceutically acceptable carrier or excipient.

In another aspect of the present disclosure is a method of reducing orameliorating symptoms of anxiety comprising administering to a subjectin need thereof a natural product composition comprising (i) acannabidiol, spikenard, valerian root, passion flow extract, andashwagandha; and (ii) a pharmaceutically acceptable carrier orexcipient. In some embodiments, the administration of the naturalproduct composition does not cause a substantial increase in serotoninlevels.

In another aspect of the present disclosure is a method of treatingdepression comprising administering to a subject in need thereof aformulation comprising a comprising (i) a cannabidiol, spikenard,valerian root, passion flow extract, and ashwagandha; and (ii) apharmaceutically acceptable carrier or excipient.

In another aspect of the present disclosure is a method of reducing orameliorating symptoms of depression comprising administering to asubject in need thereof a natural product composition comprising (i) acannabidiol, spikenard, valerian root, passion flow extract, andashwagandha; and (ii) a pharmaceutically acceptable carrier orexcipient. In some embodiments, the administration of the naturalproduct composition does not cause a substantial increase in serotoninlevels.

In another aspect of the present disclosure is a functional foodcomposition or food product comprising a cannabidiol, spikenard,valerian root, passion flow extract, and ashwagandha. In someembodiments, the food product is a gelatin (e.g. Jell-O®). In anotheraspect of the present disclosure is a dietary supplement comprisingcannabidiol, spikenard, valerian root, passion flow extract, andashwagandha.

In another aspect of the present disclosure are kits comprising anatural product composition including (i) a cannabidiol, spikenard,valerian root, passion flow extract, and ashwagandha; and (ii) apharmaceutically acceptable carrier or excipient. In some embodiments,the carrier is a food additive. In some embodiments, the kit comprisesinstructions for combining the natural product composition with the foodadditive to provide a food product comprising an effective amount of thenatural product composition active components. In some embodiments, thekit may include at least one container and at least one label. In someembodiments, suitable containers include, for example, bubble packs,boxes, bottles, vials and tubes. In some embodiments, the containers canbe formed from a variety of materials such as glass, metal or plastic.

In another aspect of the present disclosure is a composition comprising(i) an activate pharmaceutical ingredient (API) for treating ADD, ADHD,or a symptom of ADD or ADHD; and (ii) a natural product compositioncomprising (a) a cannabidiol, spikenard, valerian root, passion flowextract, and ashwagandha; and (b) a pharmaceutically acceptable carrieror excipient. In some embodiments, the API and the natural productformulation are administered contemporaneously. In some embodiments, theAPI and the natural product composition are administered sequentially.In some embodiments, co-administration of the API and the naturalproduct composition synergistically reduces at least one symptom of ADDor ADHD, or a symptom of a related disorder.

In another aspect of the present disclosure is a natural productcomposition comprising (i) a cannabidiol, (ii) a hemp oil, and (iii) atleast one additive selected from the group consisting of passion flower,a root extract from a Valerian species, Ashwagandha, and spikenard. Insome embodiments, the natural product composition further comprises atleast two of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard. In some embodiments, the natural productcomposition further comprises at least three of passion flower, a rootextract from a Valerian species, Ashwagandha, and spikenard. In someembodiments, an amount of the cannabidiol ranges from between about 2%to about 20% by total weight of the natural product composition. In someembodiments, an amount of additive ranges from between about 10% toabout 90% by total weight of the natural product composition.

In another aspect of the present disclosure is a natural productcomposition comprising a cannabidiol and at least two additives selectedfrom the group consisting of passion flower, a root extract from aValerian species, Ashwagandha, and spikenard. In some embodiments, thecomposition comprises at least three of the additives. In someembodiments, an amount of the cannabidiol ranges from between about 2%to about 20% by total weight of the natural product composition.

In another aspect of the present disclosure is a method of treatingADHD, or the symptoms thereof, comprising administering to a subject inneed thereof a formulation comprising a natural product compositioncomprising a cannabidiol and at least two additives selected from thegroup consisting of passion flower, a root extract from a Valerianspecies, Ashwagandha, and spikenard, the formulation further comprisingat least one pharmaceutically acceptable carrier. In some embodiments,the formulation is administered such that at least 4 mg/kg of thecannabidiol is administered to the subject per day. In some embodiments,the formulation is administered such that at least 6 mg/kg of thecannabidiol is administered to the subject per day. In some embodiments,the formulation is administered such that at least 8 mg/kg of thecannabidiol is administered to the subject per day.

In another aspect of the present disclosure is a method of treatinganxiety, or the symptoms thereof, comprising administering to a subjectin need thereof a formulation comprising a natural product compositioncomprising a cannabidiol and at least two additives selected from thegroup consisting of passion flower, a root extract from a Valerianspecies, Ashwagandha, and spikenard; formulation further comprising atleast one pharmaceutically acceptable carrier, and wherein theformulation is administered such that at least 4 mg/kg of thecannabidiol is administered to the subject per day.

DETAILED DESCRIPTION

Definitions

It should also be understood that, unless clearly indicated to thecontrary, in any methods claimed herein that include more than one stepor act, the order of the steps or acts of the method is not necessarilylimited to the order in which the steps or acts of the method arerecited.

As used herein, the singular terms “a,” “an,” and “the” include pluralreferents unless context clearly indicates otherwise. Similarly, theword “or” is intended to include “and” unless the context clearlyindicates otherwise. The term “includes” is defined inclusively, suchthat “includes A or B” means including A, B, or A and B.

As used herein in the specification and in the claims, “or” should beunderstood to have the same meaning as “and/or” as defined above. Forexample, when separating items in a list, “or” or “and/or” shall beinterpreted as being inclusive, i.e., the inclusion of at least one, butalso including more than one, of a number or list of elements, and,optionally, additional unlisted items. Only terms clearly indicated tothe contrary, such as “only one of or “exactly one of,” or, when used inthe claims, “consisting of,” will refer to the inclusion of exactly oneelement of a number or list of elements. In general, the term “or” asused herein shall only be interpreted as indicating exclusivealternatives (i.e. “one or the other but not both”) when preceded byterms of exclusivity, such as “either,” “one of ” “only one of” or“exactly one of ” “Consisting essentially of,” when used in the claims,shall have its ordinary meaning as used in the field of patent law.

The terms “comprising,” “including,” “having,” and the like are usedinterchangeably and have the same meaning. Similarly, “comprises,”“includes,” “has,” and the like are used interchangeably and have thesame meaning. Specifically, each of the terms is defined consistent withthe common United States patent law definition of “comprising” and istherefore interpreted to be an open term meaning “at least thefollowing,” and is also interpreted not to exclude additional features,limitations, aspects, etc. Thus, for example, “a device havingcomponents a, b, and c” means that the device includes at leastcomponents a, b and c. Similarly, the phrase: “a method involving stepsa, b, and c” means that the method includes at least steps a, b, and c.Moreover, while the steps and processes may be outlined herein in aparticular order, the skilled artisan will recognize that the orderingsteps and processes may vary.

As used herein in the specification and in the claims, the phrase “atleast one,” in reference to a list of one or more elements, should beunderstood to mean at least one element selected from any one or more ofthe elements in the list of elements, but not necessarily including atleast one of each and every element specifically listed within the listof elements and not excluding any combinations of elements in the listof elements. This definition also allows that elements may optionally bepresent other than the elements specifically identified within the listof elements to which the phrase “at least one” refers, whether relatedor unrelated to those elements specifically identified. Thus, as anon-limiting example, “at least one of A and B” (or, equivalently, “atleast one of A or B,” or, equivalently “at least one of A and/or B”) canrefer, in one embodiment, to at least one, optionally including morethan one, A, with no B present (and optionally including elements otherthan B); in another embodiment, to at least one, optionally includingmore than one, B, with no A present (and optionally including elementsother than A); in yet another embodiment, to at least one, optionallyincluding more than one, A, and at least one, optionally including morethan one, B (and optionally including other elements); etc.

As used herein, the terms “ADD” and “ADHD” are meant to encompassdisorders affecting cognitive, learning, and/or memory functions and theassociated symptoms. Included are mild cognitive impairment, attentiondeficit hyperactivity disorder, anxiety disorder, forgetfulness,impulsivity, mental fatigue, difficulty in concentration and focus.Attention Deficit Hyperactivity Disorder (ADHD) is a disorder which maybe divided into four subtypes, according to the main features associatedwith the disorder: inattentiveness, impulsivity, and hyperactivity. Thefour subtypes are ADHD predominantly impulsivity type, ADHDpredominantly inattentive type, ADHD predominantly hyperactive-impulsivetype and ADHD not otherwise specified (e.g. Attention Deficit Disorder(ADD)).

As used herein, the term “administering” means providing a composition,formulation, or specific agent to a subject in need of treatment,including those described herein.

As used herein, the term “extract” refers to an alcoholic extract, analcohol/water extract or an oil-based extract of a material, inparticular, a plant component.

The phrases “pharmaceutically acceptable” or “pharmacologicallyacceptable” refer to molecular entities and compositions that do notproduce adverse, allergic, or other untoward reactions when administeredto an animal or a human. As used herein, “pharmaceutically acceptablecarrier” includes solvents, buffers, solutions, dispersion media,coatings, antibacterial and antifungal agents, isotonic and absorptiondelaying agents and the like acceptable for use in formulatingpharmaceuticals, such as pharmaceuticals suitable for administration tohumans. The use of such media and agents for pharmaceutically activesubstances is well known in the art. Except insofar as any conventionalmedia or agent is incompatible with the expression vectors of thepresent disclosure, its use in therapeutic compositions is contemplated.

As used herein, the term “subject” refers to a mammal such as a human,mouse or primate. Typically, the mammal is a human (homo sapiens). Ahuman subject may be an adult patient or a pediatric patient.

As used herein, the terms “therapeutically effective dose” or “doseamount” refer to an amount of a composition, or a component of thecomposition, which is effective to achieve an improvement in a subjector his physiological systems including, but not limited to, improvedimprovement or elimination of symptoms, delayed onset of a disorder,slower progress of symptoms and other indicators selected as appropriateby those skilled in the art.

As used herein, the terms “treatment,” “treating,” or “treat,” withrespect to a specific condition, refer to obtaining a desiredpharmacologic and/or physiologic effect. The effect can be prophylacticin terms of completely or partially preventing a disease or symptomthereof and/or can be therapeutic in terms of a partial or complete curefor a disease and/or adverse effect attributable to the disease.“Treatment,” as used herein, covers any treatment of a disease in asubject, particularly in a human, and includes: (a) preventing thedisease from occurring in a subject which may be predisposed to thedisease but has not yet been diagnosed as having it; (b) inhibiting thedisease, i.e., arresting its development; and (c) relieving the disease,i.e., causing regression of the disease and/or relieving one or moredisease symptoms. “Treatment” can also encompass delivery of an agent oradministration of a therapy in order to provide for a pharmacologiceffect, even in the absence of a disease or condition. The term“treatment” is used in some embodiments to refer to administration of acompound of the present disclosure to mitigate a disease or a disorderin a host, preferably in a mammalian subject, more preferably in humans.Thus, the term “treatment” can include includes: preventing a disorderfrom occurring in a host, particularly when the host is predisposed toacquiring the disease but has not yet been diagnosed with the disease;inhibiting the disorder; and/or alleviating or reversing the disorder.Insofar as the methods of the present disclosure are directed topreventing disorders, it is understood that the term “prevent” does notrequire that the disease state be completely thwarted. Rather, as usedherein, the term preventing refers to the ability of the skilled artisanto identify a population that is susceptible to disorders, such thatadministration of the compounds of the present disclosure can occurprior to onset of a disease. The term does not mean that the diseasestate must be completely avoided.

Natural Product Compositions

In general, the present disclosure provides for natural productcompositions comprising at least three active components, the activecomponents selected from the group consisting of cannabidiol, spikenard,a root extract from a Valerian species, passion flower extract, andashwagandh. In some embodiments, the natural product compositioncomprises four of the active components. In other embodiments, thenatural product composition comprises all of the recited activecompounds. Each of the active components of the natural productcomposition are described herein.

Passion flower, of the family Passifloraceae, is a perennial medicinalplant used in herbal teas for its calming and sedative effect. Itincludes several hundred species, some of which, such as Passifloraedulis and Passiflora ligularis, are known to give edible fruits(passion fruit and Sweet Granadilla). Passion flower is a dry powderedherb deriving from Passiflora incarnata. Passion flower has beentraditionally used for it mild sedative effects; further, itadvantageously has a pleasant taste and is surprisingly gentle. It isbelieved that the plant contains a group of indole alkaloids and severalflavonoids which are believed responsible for its sedative and analgesiceffects.

In some embodiments, an amount of passion flower within any naturalproduct composition ranges from between about 5% to about 17.5% by totalweight of the natural product composition. In other embodiments, anamount of passion flower within any natural product composition rangesfrom between about 7.5% to about 15% by total weight of the naturalproduct composition. In yet other embodiments, an amount of passionflower within any natural product composition ranges from between about9% to about 13% by total weight of the natural product composition.

Valerian (Valeriana officinalis or Valerian edulis) is a perennial plantnative to North America, Asia and Europe. The root has beentraditionally used as treatment for anxiety and insomnia. Ameta-analysis of available studies suggest that Valerian root extractmay improve sleep absent of side-effects (Bent S, Padula A, Moore D,Patterson M, Mehling W. Valerian for sleep: a systematic review andmeta-analysis. Am J. Med. 2006 December; 119(12):1005-12 Abstract)acting particularly to decrease the time to sleep onset and improvedsleep quality in individuals. Valerian has been shown to modulate GammaAminobutyric Acid (GABA) receptors (Yuan C S, Mehendale S, Xiao Y, AungH H, Xie J T, Ang-Lee M K. The gamma-aminobutyric acidergic effects ofvalerian and valerenic acid on rat brainstem neuronal activity. AnesthAnalg. 2004 February; 98(2):353-8). Valerinic acid specifically has beenshown to decrease neural activity in the brainstem produced by the GABAreceptor antagonist, muscimol. Data from this study suggests that thepharmacological effects of valerian extract and valerenic acid aremediated through modulation of GABA(A) receptor function (Yuan C S,Mehendale S, Xiao Y, Aung H H, Xie J T, Ang-Lee M K. Thegamma-aminobutyric acidergic effects of valerian and valerenic acid onrat brainstem neuronal activity. Anesth Analg. 2004 February;98(2):353-8). Without wishing to be bound to theory, Valerian rootextract product causes the release of gamma-aminobutyric acid (GABA) andinhibits the action of GABA transaminase, the enzyme that destroys theneurotransmitter.

In some embodiments, the formulation comprises a root extract from aValerian species, e.g. Valerian officinalis or Valerian edulis. In someembodiments, an amount of a root extract from a Valerian species withinany natural product composition ranges from between about 30% to about60% by total weight of the natural product composition. In otherembodiments, an amount of a root extract from a Valerian species withinany natural product composition ranges from between about 35% to about55% by total weight of the natural product composition. In yet otherembodiments, an amount of a root extract from a Valerian species withinany natural product composition ranges from between about 40% to about50% by total weight of the natural product composition.

Ashwagandha (Withania somnifera) is an erect shrub found growing wildthroughout the hotter parts of India and is cultivated for its roots,which are well known in Ayurveda for their rejuvenative or rasayanaproperties. Without wishing to be bound by any particular theory, it isbelieved that the roots contain between about 0.2 and about 0.3% ofalkaloids and withaferin A together with several withanolides, which areC-28 steroidal lactones of the ergostane type. In addition, the rootsare believed to contain starch, reducing sugars, hentriacontane(C31-normal alkane), and a number of amino acids. Also present aresitoindosides VII and VIII, which are acylsteryl glucosides, andsitoindosides IX and X, which are C-28 glycowithanolides that maycontribute to the adaptogenic properties found in this herb. There areseveral chemotypes of the plant Ashwagandha (Withania somnifera)available with varying amounts of the various sitoindosides. See, M S.Premila (2007), Ayurvedic Herbs.

Ashwagandha (Withania somnifera) root powder, root methanol extract, andits active principles (a mixture containing equimolar concentrations ofwithaferin A and sitoindosides VII-X), have been shown to possessantioxidant activity, which may explain the antistress,anti-inflammatory, immunomodulatory, and cognition-enhancing andrejuvenative effects shown in experimental and clinical studies.Withaferin A has been shown to have anti-inflammatory and antiarthriticproperties in several experimental models. See, M S. Premila (2007),Ayurvedic Herbs. Ashwagandha herb can be provided, for example, inAshwagandha root extract powder, standardized to greater than 5%withanolides by weight.

In some embodiments, an amount of Ashwagandha within any natural productcomposition ranges from between about 10% to about 30% by total weightof the natural product composition. In other embodiments, an amount ofAshwagandha within any natural product composition ranges from betweenabout 15% to about 27.5% by total weight of the natural productcomposition. In yet other embodiments, an amount of Ashwagandha withinany natural product composition ranges from between about 20% to about25% by total weight of the natural product composition.

Spikenard (Nardostachys jatamanse) is a class of aromatic amber-coloredessential oil. Without wishing to be bound by any particular theory,spikenard is considered a calming herb in ayurveda and unani because ofits medicinal values. In ayurveda, it is often used against stress,spasm, epilepsy, convulsion and hysteria.

In some embodiments, an amount of spikenard within any natural productcomposition ranges from between about 5% to about 20% by total weight ofthe natural product composition. In other embodiments, an amount ofspikenard within any natural product composition ranges from betweenabout 7.5% to about 17.5% by total weight of the natural productcomposition. In yet other embodiments, an amount of spikenard within anynatural product composition ranges from between about 10% to about 15%by total weight of the natural product composition.

Without wishing to be bound by any particular theory, it is believedthat cannabidiol (“CBD”) is non-psychoactive and may act as ananti-inflammatory agent. CBD is a compound belonging to a broader classof cannabinoids. Cannabinoids are a heteromorphic group of chemicalswhich activate the body's cannabinoid receptors. Initially cannabinoidswere discovered in Cannabis sativa, the cannabis plant. There are threemain types of cannabinoids: herbal cannabinoids that occur uniquely inthe cannabis plant, synthetic cannabinoids that are manufactured andendogenous cannabinoids that are produced in vivo. Herbal cannabinoidsare nearly insoluble in water but soluble in lipids, alcohol andnon-polar organic solvents. These natural cannabinoids are concentratedin a viscous resin that is produced in glandular structures known astrichomes. In addition to cannabinoids, the resin is rich in terpenes,which are largely responsible for the odor of the cannabis plant.

Unlike cannabinoids (e.g. THC), cannabidiols do not bind either thebrain receptor CB1 or the peripheral receptors CB2 and therefore doesnot cause the central or peripheral effects mediated by these receptors.Furthermore, CBD has no psychotropic (cannabimimetic) activity and itsmolecular structure and properties are substantially different fromthose of cannabinoids [Science 169: 611-612 (1970);“Marijuana/cannabinoids: neurobiology and neurophysiology,” ed. L.Murphy and A. Bartke, CRC Press, Boca Raton, 1-33 (1992)].

In addition to its immunomodulating and anti-inflammatory properties,CBD has been reported to exhibit anticonvulsive, anti-anxiety, andantipsychotic activity, and function as an efficient neuroprotectiveantioxidant. The in vitro suppressive effect of CBD on down-modulatingthe release of tumor necrosis factor α (TNFα), interleukin 1 (IL-1), andinterferon γ (IFN)-γ from peripheral blood cells has also been reported.CBD has demonstrated activity in ameliorating collagen-induced arthritisin mice and has been shown to suppress T-cell responses and theproduction of TNFα and IFNγ. CBD also inhibits uptake of THC andanandamide and its hydrolysis. For example, U.S. Pat. No. 6,410,588describes the use of cannabidiol for treating inflammatory diseases suchas rheumatoid arthritis, multiple sclerosis and Crohn's Disease, andmedicinal preparations containing CBD for use in treating such diseases.By means of another example, PCT/IL01/00537 describes pharmaceuticalcompositions comprising cannabidiol derivatives which have analgesic,antianxiety, anticonvulsive, neuroprotective, antipsychotic andanticancer activity.

In some embodiments, cannabidiol refers to2-[3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediolas well as to pharmaceutically acceptable salts, solvates, metabolites(e.g., cutaneous metabolites), and metabolic precursors of2-[3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol.The synthesis of2-[3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediolis described, for example, in Petilka et al., Hely. Chim. Acta, 52:1102(1969) and in Mechoulam et al., J. Am. Chem. Soc., 87:3273 (1965), whichare hereby incorporated by reference.

In some embodiments, an amount of cannabidiol within any natural productcomposition ranges from between about 2% to about 20% by total weight ofthe natural product composition. In other embodiments, an amount ofcannabidiol within any natural product composition ranges from betweenabout 4% to about 15% by total weight of the natural productcomposition. In yet other embodiments, an amount of cannabidiol withinany natural product composition ranges from between about 6% to about11% by total weight of the natural product composition.

In some embodiments, a natural product composition comprises (i) passionflower in an amount ranging from between about 5% to about 17.5% bytotal weight of the natural product composition; (ii) a root extractfrom a Valerian species in an amount ranging from between about 30% toabout 60% by total weight of the natural product composition; (iii)Ashwagandha in an amount ranging from between about 10% to about 30% bytotal weight of the natural product composition; (iv) spikenard in anamount ranging from between about 5% to about 20% by total weight of thenatural product composition; and (v) cannabidiol in an amount rangingfrom between about 2% to about 20% by total weight of the naturalproduct composition.

Pharmaceutically Acceptable Excipients, Carriers, and Additives

The compositions of the present disclosure may further comprise one ormore pharmaceutically acceptable excipients including, but not limitedto, diluents, binders, lubricants, disintegrants, flavoring agents,taste-masking agents, coloring agents, pH modifiers, stabilizers,absorption enhancers, viscosity modifiers, film forming polymers,bulking agents, surfactants, glidants, plasticizers, preservatives,essential oils and sweeteners. In some embodiments, the pharmaceuticallyacceptable excipients, carriers, and/or additives may be a foodcomposition or a food product into which the natural productcompositions described herein may be introduced.

A person skilled in the art will be able to select the suitableexcipients or mixtures of excipients for the desired natural productcomposition. In general, the amount of any pharmaceutically acceptableexcipient, carrier, and/or additive included within any natural productcomposition may vary depending on the desired effect, route ofadministration, form of the final composition. In general, however, atotal amount of pharmaceutically acceptable excipients, carriers, and/oradditives formulated with the natural product compositions may rangefrom about 1% to about 99% by total weight of the composition. In otherembodiments, the total amount of pharmaceutically acceptable excipients,carriers, and/or additives formulated with the natural productcompositions may range from about 1% to about9% by total weight of thecomposition. In other embodiments, the total amount of pharmaceuticallyacceptable excipients, carriers, and/or additives formulated with thenatural product compositions may range from about 1% to about 80% bytotal weight of the composition. In yet other embodiments, the totalamount of pharmaceutically acceptable excipients, carriers, and/oradditives within the natural product compositions may range from about1% to about 50% by total weight of the composition. In otherembodiments, the total amount of pharmaceutically acceptable excipients,carriers, and/or additives formulated with the natural productcompositions may range from about 5% to about 50% by total weight of thecomposition. By way of example only, a formulation may comprise a 50:50mixture of any of a natural product composition and a pharmaceuticallyacceptable excipient, carrier, and/or additive.

In some embodiments, a ratio of an amount of a natural productcomposition and an amount of a pharmaceutically acceptable excipient orcarrier ranges from about 100:1 to about 1:100. In some embodiments, aratio of an amount of a natural product composition and an amount of apharmaceutically acceptable excipient or carrier ranges from about 50:1to about 1:50. In some embodiments, a ratio of an amount of a naturalproduct composition and an amount of a pharmaceutically acceptableexcipient or carrier ranges from about 25:1 to about 1:25. In someembodiments, a ratio of an amount of a natural product composition andan amount of a pharmaceutically acceptable excipient or carrier rangesfrom about 10:1 to about 1:10. In some embodiments, a ratio of an amountof a natural product composition and an amount of a pharmaceuticallyacceptable excipient or carrier ranges from about 5:1 to about 1:5.

In some embodiments, the carrier is water. In some embodiments, anamount of water present in the composition ranges from about 90% toabout 98% by total weight of the composition, from about 90% to about97% by total weight of the composition, from about 90% to about 96% bytotal weight of the composition, from about 90% to about 95% by totalweight of the composition, from about 90% to about 94% by total weightof the composition, from about 90% to about 93% by total weight of thecomposition, from about 90% to about 92% by total weight of thecomposition, and from about 90% to about 91% by total weight of thecomposition.

A diluent may be selected from, for example, calcium carbonate, calciumphosphate dibasic, calcium phosphate tribasic, calcium sulfate,microcrystalline cellulose, microcrystalline silicified cellulose,powdered cellulose, dextrate, dextrose, fructose, lactitol, lactoseanhydrous, lactose monohydrate, lactose dihydrate, lactose trihydrate,mannitol, sorbitol, starch, pregelatinized starch, sucrose, talc,xylitol, maltose, maltodextrin, maltitol.

A binder may be selected from, for example, acacia, alginic acid,carbomer, carboxymethylcellulose calcium, carbomethylcellulose sodium,microcrystalline cellulose, powdered cellulose, ethyl cellulose, gelatinliquid glucose, guar gum, hydroxyethyl cellulose, hydroxypropylcellulose, hydroxypropylmethyl cellulose, maltodextrin, methylcellulose,polydextrose, polyethtylene oxide, povidone, sodium alginate, starchpaste, pregelatinized starch, sucrose, tragacanth, low-substitutedhydroxypropyl cellulose, glucose, sorbitol.

A suitable filler may be selected from, for example, starch derivatives,such as corn starch, potato starch or rice starch, polysaccharides suchas dextrins, maltodextrins, dextrates, microcrystalline cellulose,powdered cellulose, mixture of microcrystalline cellulose and guar gum,coprocessed blends of microcrystalline cellulose; and polyhydricalcohols, such as xylitol and sorbitol.

A disintegrant may be selected from, for example, alginic acid, carbondioxide, carboxymethylcellulose calcium, carboxymethylcellulose sodium,microcrystalline cellulose, powdered cellulose, croscarmelose sodium,crospovidone, sodium docusate, gaur gum, hydroxypropyl cellulose,methylcellulose, polacrilin potassium, poloxamer, povidone, sodiumalginate, sodium glycine carbonate, sodium lauryl sulfate, sodium starchglycolate, starch, pregelatinized starch, low-substituted hydroxypropylcellulose.

A glidant may be selected from, for example, calcium silicate, powderedcellulose, starch, talc, colloidal silicon dioxide.

A lubricant may be selected from, for example, magnesium stearate,stearic acid, sodium stearyl fumarate, magnesium lauryl sulphate, talc,polyethylene glycol, and glyceryl behenate.

A suitable essential oil may be selected from Bergamot oil (extractedfrom Citrus aurantium L. subsp. bergamia Wright et Am.); Ylang ylang oil(extracted from Cananga odorata Hook. f. and Thoms.); Jasmine essentialoil (extracted from Jasminum officinale L.). In one embodiment, amixture of essential oils comprises equal portions totaling about 0.01%to about 1% w/w, preferably about 0.1% w/w of the total composition.Other essential oils are possible.

A suitable sweetener may be selected from sugars such as sucrose,lactose and glucose; cyclamate and salts thereof; saccharin and saltsthereof; and aspartame.

Flavoring agents may be incorporated in the composition may be chosenfrom synthetic flavors oils and flavoring aromatics, natural oils, plantextracts. Examples include cinnamon oil, oil of wintergreen, peppermintoil, clove oil, bay oil, anise oil, eucalyptus, thyme oil, cedar leafoil, nutmeg oil, sage oil or almond oil. Examples of flavoring agentsinclude, but are not limited to, almond, apple, banana, berry,bubblegum, caramel, citrus, cherry, chocolate, coconut, grape, greentea, honey, lemon, licorice, lime, mango, maple, mint, orange, peach,pineapple, raisin, strawberry, vanilla, watermelon and combinationsthereof. Flavors may be present in an amount ranging from about 0.05 toabout 3 percent by weight based upon the weight of the composition. Insome embodiments, the flavoring agent may be selected from natural orsynthetic flavors such as, for example, strawberry flavor, wild cherryflavor, green apple flavor, spearmint flavor and peppermint flavor.

Absorption enhancers for use in accordance with certain embodiments ofthe present disclosure include, for example, Gelucire 44/14; Gelucire50/13; Tagat TO; Tween 80; isopropyl myristate, polysorbates, sorbitanesters, poloxamer block copolymers, PEG-35 castor oil, PEG-40hydrogenated castor oil, caprylocaproyl macrogol-8 glycerides, PEG-8caprylic/capric glycerides, sodium lauryl sulfate, dioctylsulfosuccinate, polyethylene lauryl ether, ethoxydiglycol, propyleneglycol mono-di-caprylate, glycerol monocaprylate, glyceryl fatty acids(C8-C18) ethoxylated, oleic acid, linoleic acid, glycerylcaprylate/caprate, glyceryl monooleate, glyceryl monolaurate,caprylic/capric triglycerides, ethoxylated nonylphenols, PEG-(8-50)stearates, olive oil PEG-6 esters, triolein PEG-6 esters, lecithin,d-alpha tocopheryl polyethylene glycol 1000 succinate, polycarbonate,sodium glycocholate, sodium taurocholate, cyclodextrins, citric acid,sodium citrate, triacetin, combinations thereof, and the like. Incertain preferred embodiments, the absorption enhancer is triacetin. Incertain embodiments where an absorption enhancer is included in theformulation, the absorption enhancer is included in an amount of fromabout 0.001% to about 10% by weight of the formulation, preferably in anamount of about 0.01% to about 5% by weight of the formulation.

Routes of Administration and Dosage Forms

Administration to a subject of the natural product compositionsaccording to the present disclosure may be via any common route so longas the target tissue is available via that route. The natural productcompositions may conveniently be presented in dosage unit form and maybe prepared by any of the methods well known in the art of pharmacy. Allmethods include the step of bringing the natural product composition (orthe individual components thereof) into association with an excipient orcarrier. In general, the natural product compositions are prepared byuniformly and intimately bringing the active components into associationwith a liquid carrier or a finely divided solid carrier or both, andthen, if necessary, shaping the product into the desired dosage form. Inthe natural product compositions, the active components are included inan amount sufficient to produce the desired pharmacologic effect.

Food Products

A food product, dietary composition or supplement according to thepresent disclosure is any ingestible preparation that contains thenatural product compositions of the present disclosure mixed with a foodproduct or dietary supplement composition. The food product can bedried, cooked, boiled, lyophilized or baked. A food composition or foodproduct can comprise a bakery product, including but not limited tobread, pastries, brownies, cakes, pies, donuts, crackers, and muffins. Afood composition or food product can comprise a dairy product, includingbut not limited to milk, fermented milk, curd, whey, yogurt, cream,cheese, butter, clarified butter, ghee, and ice cream. A foodcomposition or food product can comprise a nut butter or seed butter,including but not limited to peanut butter, almond butter, cashewbutter, hazelnut butter, macadamia nut butter, pecan butter, pistachiobutter, walnut butter, pumpkin seed butter, sesame seed butter, soybeanbutter, and sunflower seed butter. A food composition or food productcan comprise an oil (e.g., a cooking oil), including but not limited toolive oil, coconut oil, vegetable oil, canola oil, corn oil, peanut oil,sunflower seed oil, almond oil, avocado oil, rice bran oil, cottonseedoil, flaxseed oil, linseed oil, grape seed oil, hemp oil, mustard oil,macadamia oil, palm oil, tea seed oil, walnut oil, margarine, lard,butter, clarified butter, ghee, or tallow. A food composition or foodproduct can comprise sports food products such as energy gels, sportsdrinks, energy powders, energy bars, energy shots, protein powders, andprotein drinks (e.g., protein shakes). A food composition or foodproduct can comprise a beverage, including but not limited to water,electrolyte drinks, soda, coconut water, tea (e.g., Jun tea, black tea,green tea, white tea, herbal tea), coffee, a soft drink, an alcoholicbeverage (e.g., cocktail, liquor, spirits, beer, wine, malt beverage),water, juice (e.g., apple juice, orange juice, tomato juice, vegetablejuice, cranberry juice), a sports drink, electrolyte-enriched water,vitamin-enhanced water, milk (e.g., dairy-based milk, coconut milk,almond milk, soy milk, hemp milk, rice milk, oat milk, cashew milk,hazelnut milk), and yogurt.

A food composition or food product may include the natural productcomposition disclosed herein within a gelatin-based product (e.g.Jell-O®) or gelatin-based desert. In some embodiments, the foodcomposition or food product comprises the natural product compositionand a gelling agent. Suitable examples of gelling agents includecarrageenans, agar, sodium alginate, gellan gum, xanthan gum, sodiumcarboxymethyl cellulose, guar gum, soybean protein, and crystallinecellulose. The amount of the gelling agent contained within the foodcomposition or food product is not limited provided that the effect ofthe present disclosure is obtained. The proportion of the gelling agentin the food composition is, for example, about 0.5 to about 3 by totalweight of the food composition or food product. Without wishing to bebound by any particular theory, it is believed that the amount of thegelling agent contained affects the hardness in mastication. If theamount of gelling agent is less than about 0.5 by total weight of thefood composition or food product, the food composition or food producttends to become overly soft, and cannot achieve a hardness suitable formastication. If, on the other hand, the amount is more than about 3 bytotal weight of the food composition or food product, the foodcomposition or food products tends to fail to achieve a hardness atwhich chewing can be performed, even if the number of mastications isincreased.

In some embodiments, food products are specifically formulated forpediatric patients, thereby providing a dosage form that is appealing tothe patient. For example, a food product may comprise a gelatin-basedproduct whereby a suitable pediatric dose of a natural productcomposition is contained therein, along with flavoring agents and/oragents that create a desirable mouthfeel. In this way, it is believedthat administration to a pediatric patient may be facilitated. It isalso believed that such a food product avoids additional stressesassociated with taking liquid dosage forms which may have unpleasanttastes, aftertastes, or textures. It is also believed that such a foodproduct avoids the need for swallowing a solid dosage form, which may bedifficult for a pediatric patient.

Oral Dosage Forms

The natural product compositions containing the active components may beprovided, in general, in the form of discrete units such as hard or softcapsules, tablets, troches or lozenges, each containing a predeterminedamount of the active components; in the form of a dispersible powder orgranules; in the form of a solution or a suspension in an aqueous liquidor non-aqueous liquid; in the form of syrups or elixirs; or in the formof an oil-in-water emulsion or a water-in-oil emulsion.

Liquid dosage forms for oral administration include, but are not limitedto, pharmaceutically acceptable emulsions, solutions, suspensions,syrups and elixirs. In addition to the natural product compositionsactive components described herein, any liquid dosage forms may containinert diluents commonly used in the art. For instance, liquidformulations can contain water, alcohol, polyethylene glycol ethers, orany other pharmaceutically acceptable solvents. Solubilizing agents andemulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate,ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol,1,3-butylene glycol, dimethyl formamide, oils (in particular,cottonseed, groundnut, corn, germ, olive, castor, and sesame oils),glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fattyacid esters of sorbitan, and mixtures thereof may also be present in theinventive compositions. Additionally, oral compositions can includeadjuvants such as wetting agents, emulsifying and suspending agents,sweetening, flavoring, and perfuming agents. When formulated as asuspension, the inventive compositions contain the cannabinoid extractand suspending agents, for example, ethoxylated isostearyl alcohols,polyoxyethylene sorbitol, sorbitan esters, microcrystalline cellulose,aluminum metahydroxide, bentonite, agar-agar, tragacanth, and mixturesthereof.

Aqueous suspensions normally contain the natural product compositionactive components in admixture with excipients suitable for themanufacture of aqueous suspensions. Such excipients may be (a)suspending agents such as hydroxy ethylcellulose, sodiumcarboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose,sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia;(b) dispersing or wetting agents which may be (b.1) anaturally-occurring phosphatide such as lecithin, (b.2) a condensationproduct of an alkylene oxide with a fatty acid, for example,polyoxyethylene stearate, (b.3) a condensation product of ethylene oxidewith a long chain aliphatic alcohol, for exampleheptadecaethyleneoxycetanol, (b.4) a condensation product of ethyleneoxide with a partial ester derived from a fatty acid and a hexitol suchas polyoxyethylene sorbitol monooleate, or (b.5) a condensation productof ethylene oxide with a partial ester derived from a fatty acid and ahexitol anhydride, for example polyoxyethylene sorbitan monooleate.

The aqueous suspensions may also contain one or more preservatives, forexample, ethyl or n-propyl p-hydroxybenzoate; one or more coloringagents; one or more flavoring agents; and one or more sweetening agents,such as sucrose or saccharin.

Oily suspensions may be formulated by suspending the natural productcomposition active components in a vegetable oil, for example arachisoil, olive oil, sesame oil or coconut oil, or in a mineral oil such asliquid paraffin. The oily suspensions may contain a thickening agent,for example beeswax, hard paraffin or cetyl alcohol. Sweetening agentsand flavoring agents may be added to provide a palatable oralpreparation. These compositions may be prepared by the addition of anantioxidant such as ascorbic acid.

Dispersible powders and granules are suitable for the preparation of anaqueous suspension. They provide the natural product composition activecomponents separately in admixture with a dispersing or wetting agent, asuspending agent and one or more preservatives. Suitable dispersing orwetting agents and suspending agents are exemplified by those alreadydescribed herein. Additional excipients, for example, those sweetening,flavoring and coloring agents described above may also be present,including each of those described herein.

The pharmaceutical compositions of the disclosure may also be in theform of oil-in-water emulsions. The oily phase may be a vegetable oilsuch as olive oil or arachis oils, or a mineral oil such as liquidparaffin or a mixture thereof.

Suitable emulsifying agents may be (a) naturally-occurring gums such asgum acacia and gum tragacanth, (b) naturally-occurring phosphatides suchas soybean and lecithin, (c) esters or partial esters derived from fattyacids and hexitol anhydrides, for example, sorbitan monooleate, (d)condensation products of said partial esters with ethylene oxide, forexample polyoxyethylene sorbitan monooleate. The emulsions may alsocontain sweetening and flavoring agents.

Syrups and elixirs may be formulated with sweetening agents, forexample, glycerol, propylene glycol, sorbitol or sucrose. Suchformulations may also contain a preservative and flavoring and coloringagents.

Solid dosage forms suitable for oral administration include, capsules,tablets, pills, powders, and granules. The natural product compositionsdisclosed herein may also be formulated into candies, lollipops,lozenges, etc. In such solid dosage forms, the natural productcompositions may be mixed with at least one pharmaceutically acceptableexcipient or carrier such as sodium citrate or dicalcium phosphateand/or a) fillers or extenders such as starches, lactose, sucrose,glucose, mannitol, and silicic acid, b) binders such as, for example,carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone,sucrose, and acacia, c) humectants such as glycerol, d) disintegratingagents such as agar-agar, calcium carbonate, potato or tapioca starch,alginic acid, certain silicates, and sodium carbonate, e) solutionretarding agents such as paraffin, f) absorption accelerators such asquaternary ammonium compounds, g) wetting agents such as, for example,acetyl alcohol and glycerol monostearate, h) absorbents such as kaolinand bentonite clay, and i) lubricants such as talc, calcium stearate,magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate,and mixtures thereof. For capsules, tablets and pills, the dosage formcan also comprise buffering agents.

In some embodiments, natural product compositions for oral use may be inthe form of hardgelatin or HPMC capsules wherein the active componentsare mixed with an inert solid diluent, for example pregelatinizedstarch, calcium carbonate, calcium phosphate or kaolin, or dispensed viaa pellet formulation. They may also be in the form of soft gelatincapsules wherein the active ingredient is mixed with water or an oilmedium, for example peanut oil, liquid paraffin, medium chaintriglycerides or olive oil. A medium chain triglyceride or MCT as thatterm is used herein, refers to a saturated fat containing from 6-12carbon atoms. More particularly MCTs comprise substantially 100% C8-C10fatty acid triglycerides. MCTs are preferably produced by esterifyingglycerol with medium chain fatty acids. MCT materials useful in theinvention are available, for example, from the Stepan Company ofNorthfield, Ill. under the trademark NEOBEE®, e.g., NEOBEE® 1095. Otherexamples of MCT oil to be used in the compositions of the presentinvention are TCM (trade name) being a mixture of triglycerides whereinabout 95% (w/v) of the fatty acid chains have either 8 or 10 carbonatoms Societe des Oleagineaux, France), Miglyol 812 (trade name being amixed triester of glycerine and caprilic and capric acids-Dynamit Nobel,Sweden).

The tablets, capsules or pellets may be uncoated or they may be coatedby known techniques to delay disintegration and absorption in thegastrointestinal tract and thereby provide a delayed action or sustainedaction over a longer period. For example, a time delay material such ascelluloseacetate phtalate or hydroxypropylcellulose acetate succinate orsustained release material such as ethylcellulose or ammoniomethacrylatecopolymer (type B) may be employed.

Topical Administration

Dosage forms for topical administration include, but are not limited to,ointments, creams, emulsions, lotions, gels, sunscreens and agents thatfavor penetration within the epidermis. Various additives, known tothose skilled in the art, may be included in the topical formulations ofthe present disclosure. Examples of additives include, but are notlimited to, solubilizers, skin permeation enhancers, preservatives(e.g., anti-oxidants), moisturizers, gelling agents, buffering agents,surfactants, emulsifiers, emollients, thickening agents, stabilizers,humectants, dispersing agents and pharmaceutical carriers. Examples ofmoisturizers include jojoba oil and evening primrose oil. Suitable skinpermeation enhancers are well known in the art and include loweralkanols, such as methanol ethanol and 2-propanol; alkyl methylsulfoxides such as dimethylsulfoxide (DMSO), decylmethylsulfoxide (C10MSO) and tetradecylmethyl sulfoxide; pyrrolidones, urea;N,N-diethyl-m-toluamide; C₂-C₆ alkanediols; dimethyl formamide (DMF),N,N-dimethylacetamide (DMA) and tetrahydrofurfuryl alcohol. Examples ofsolubilizers include, but are not limited to, hydrophilic ethers such asdiethylene glycol monoethyl ether (ethoxydiglycol, availablecommercially as Transcutol®) and diethylene glycol monoethyl etheroleate (available commercially as Softcutol®); polyoxy 35 castor oil,polyoxy 40 hydrogenated castor oil, polyethylene glycol (PEG),particularly low molecular weight PEGs, such as PEG 300 and PEG 400, andpolyethylene glycol derivatives such as PEG-8 caprylic/capric glycerides(available commercially as Labrasol®); alkyl methyl sulfoxides, such asDMSO; pyrrolidones, DMA, and mixtures thereof.

Vape Compositions, Vapor Phase Compositions, or Inhalable Compositions

In some embodiments, the dosage form is a vape composition, such as forpulmonary administration. In some embodiments, the vape compositionincludes one or more polyols. Examples of suitable polyols include1,3-butanediol (e.g., racemic), 1,2-butanediol (e.g., racemic),2,3-butanediol (e.g., racemic), 1,2,5-pentanetriol (e.g., racemic),1,3,5-pentanetriol (e.g., racemic), 2,4-pentanediol (e.g., racemic),1,2-pentanediol (e.g., racemic), and 1,2,6-hexanetriol (e.g., racemic).Based in part on their low toxicity (LD50), the polyols serve asdesirable, low-boiling-point alternatives to propylene glycol. Further,their characteristics also serve to offset the need for1,2,3-propanetriol as a co-excipient commonly found in vapingexcipients. In an embodiment, the compositions do not solely comprisepropane-1,2-diol and/or 1,2,3-propanetriol. In another embodiment, thecompositions do not comprise propane-1,2-diol and/or 1,2,3-propanetriol.Polyols are commercially available or can be manufactured using methodsknown in the art.

In various embodiments, the polyol is a tetraol (e.g., (2R, 3S)butane-1,2, 3,4-tetraol (erythritol) and (2R,3R)-butane-1,2,3,4-tetraol(threitol)), a pentol (e.g., (2R,4R)-pentane-1,2,3,4,5-pentol(arabitol), (2R,45)-pentane-1,2,3,4,5-pentol (xylitol), (2R,3S,4S)-pentane-1,2,3,4,5-pentol (ribitol), and (2R,3S, 4R,5(S)-hexane-1,2,3, 4,5-pentol (fucitol)), a hexol (e.g.,(2R,3R,4R,5R)-hexan-1,2,3,4,5,6-hexol (mannitol),(2S,3R,4R,5R)-hexane-1,2,3,4,5,6-hexol (sorbitol), (2R,3{circumflex over( )},4R,55)-hexane-1,2,3,4,5,6-hexol (galactitol),and(2R,3S,4S,5R)-hexane-1,2,3,4,5,6-hexol “iditol”)), a heptol (e.g.,(2R,3R,5R,6R)-heptane-1,2,3,4,5,6,7-heptol (volemitol) and(2S,35′,55′,65)-heptane-1,2,3,4,5,6,7-heptol (perseitol)).

In some embodiments, the polyol is a polyol ether. Examples of suitablepolyol ethers include isomalt((2R,3R,4R,5R)-6-[[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)-2-tetrahydropyranyl]oxy]hexane-1,2,3, 4,5-pentol), lactitol (4-O-a-D-galactopyranosyl-D-glucitol), andmaltitol (4-O-a-D-glucopyranosyl-D-glucitol).

The vape compositions may also include one or more solubilizingcompounds (also referred to herein as co-solute compounds). Thesolubilizing compounds may also be active compounds. The solubilizingcompounds are polar (e.g., modestly polar compounds), non-polar, orcomplex non-polar compounds that increase the solubility of the one ormore active compounds in the composition. The solubilizing compounds maybe planar and have both polar and nonpolar regions that reducehydrophobic interactions. Without intending to be bound by anyparticular theory, it is considered that the solubilizing compound formsadducts with the polyol(s) and/or disruptive compound(s). Compositionscomprising on or more solubilizing compounds may form hydrotropes.Combinations of solubilizing compounds may be used in the compositions.The solubilizing compounds may be present in the compositions at 1 to 40mol %, including all integer mol % values and ranges there between.

In some embodiments, the vape composition includes one or moreflavorants in an amount ranging from about 0.01% to about 15% by totalweight (e.g., about 1% to about 12%, about 2% to about 10%, or about 5%to about 8%) of the vape composition.

In some embodiments, the vape compositions described herein include anatural product composition (such as described herein) and awater-miscible solvent, including, but not limited to, selected from thegroup consisting of propylene glycol, glycerol, ethanol and acombination thereof. Propylene glycol, having a boiling point of 188.2°C. and glycerol having a boiling point of 290° C., act as solvents andas thickening agents. Propylene glycol, glycerol and ethanol alsoprovide a relatively even heating of the inhalable composition as it isvaporized by the apparatus.

In some embodiments, the vape compositions include about 0 wt. %, 1 wt.%, 2 wt. %, 3 wt. %, 4 wt. %, 5 wt. %, 6 wt. %, 7 wt. %, 8 wt. %, 9 wt.%, 9.5 wt. %, 10 wt. %, 10.5 wt. %, 11 wt. %, 12 wt. %, 13 wt. %, 14 wt.%, 15 wt. %, 16 wt. %, 17 wt. %, 18 wt. %, 19 wt. %, 20 wt. %, 30 wt. %,40 wt. %, 50 wt. % or a percentage between any two of these values ofpropylene glycol relative to the of the entire vape composition. In someembodiments, the inhalable composition comprises propylene glycol anddoes not contain glycerol.

In some embodiments, a quantity of glycerol that is added to the vapecompositions comprises 0 wt. %, 1 wt. %, 2 wt. %, 3 wt. %, 4 wt. %, 5wt. %, 6 wt. %, 7 wt. %, 8 wt. %, 9 wt. %, 9.5 wt. %, 10 wt. %, 10.5 wt.%, 11 wt. %, 12 wt. %, 13 wt. %, 14 wt. %, 15 wt. %, 16 wt. %, 17 wt. %,18 wt. %, 19 wt. %, 20 wt. %, 30 wt. %, 40 wt. %, 50 wt. % or apercentage between any two of these values of glycerol relative to theof the entire vape composition. In some embodiments, the inhalablecomposition comprises glycerol and does not contain propylene glycol.

In some embodiments, a quantity of ethanol that is added to the vapecompositions comprises 0 wt. %, 1 wt. %, 2 wt. %, 3 wt. %, 4 wt. %, 5wt. %, 6 wt. %, 7 wt. %, 8 wt. %, 9 wt. %, 9.5 wt. %, 10 wt. %, 10.5 wt.%, 11 wt. %, 12 wt. %, 13 wt. %, 14 wt. %, 15 wt. %, 16 wt. %, 17 wt. %,18 wt. %, 19 wt. %, 20 wt. %, 30 wt. %, 40 wt. %, 50 wt. % or apercentage between any two of these values of ethanol relative to the ofthe entire vape composition. In some embodiments, the inhalablecomposition comprises ethanol and does not contain glycerol or propyleneglycol.

In some embodiments, the vape composition described herein comprisespropylene glycol and glycerol, each in any of the wt % amounts describedherein, such that the vape composition has a wt/wt % ratio of propyleneglycol to glycerol (i.e., propylene glycol:glycerol) of 1:1,000, 1:500,1:100, 1:50, 1:25, 1:20, 1:15, 1:10, 1:5, 1:4, 1:3, 1:2, 1.1.5, 1:1.4,1:1.3, 1:1.2, 1:1.1, 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 2:1, 3:1,4:1, 5:1, 10:1, 15:1, 20:1, 25:1, 50:1, 100:1, 1,000:1 or a ratiobetween any two of these values. In some embodiments, the vapecomposition comprises propylene glycol and glycerol, and the vapecomposition has a ratio of propylene glycol to glycerol of about 2:1 toabout 1:2.

In some embodiments, the vape composition described herein comprisespropylene glycol and ethanol, each in any of the wt % amounts describedherein, such that the vape composition has a wt/wt % ratio of propyleneglycol to ethanol (i.e., propylene glycol:ethanol) of 1:1,000, 1:500,1:100, 1:50, 1:25, 1:20, 1:15, 1:10, 1:5, 1:4, 1:3, 1:2, 1.1.5, 1:1.4,1:1.3, 1:1.2, 1:1.1, 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 2:1, 3:1,4:1, 5:1, 10:1, 15:1, 20:1, 25:1, 50:1, 100:1, 1,000:1 or a rationbetween any two of these values. In some embodiments, the vapecomposition comprises propylene glycol and ethanol, and the vapecomposition has a ratio of propylene glycol to ethanol of about 2:1 toabout 1:2.

In some embodiments, the vape composition described herein comprisesethanol and glycerol, each in any of the wt % amounts described herein,such that the vape composition has a wt/wt % ratio of ethanol toglycerol (i.e., ethanol:glycerol) of 1:1,000, 1:500, 1:100, 1:50, 1:25,1:20, 1:15, 1:10, 1:5, 1:4, 1:3, 1:2, 1.1.5, 1:1.4, 1:1.3, 1:1.2, 1:1.1,1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 2:1, 3:1, 4:1, 5:1, 10:1, 15:1,20:1, 25:1, 50:1, 100:1, 1,000:1 ora ration between any two of thesevalues. In some embodiments, the vape composition comprises ethanol andglycerol, and the vape composition has a ratio of ethanol to glycerol ofabout 2:1 to about 1:2.

Other inhalable compositions or components suitable for formulating thenatural product formulations (such as those disclosed herein) intoinhalable compositions or vape compositions include those described inUnited States Patent Application Nos. 2017/0341850, 2017/0079322,2015/0013695, 2014/0377355, 2014/0377357, and 2015/0297516, thedisclosures of which are each hereby incorporated by reference herein intheir entireties.

Dosing and Dosing Schedules

One of ordinary skill will appreciate that effective amounts of thecomponents in the formulations used in the methods of the presentdisclosure can be determined empirically. It will be understood that,when administered to a patient, the total daily usage of the formulationof the present disclosure will be decided by the attending physician orother medical professional within the scope of sound medical judgment.The specific therapeutically effective dose level for any patient willdepend upon a variety of factors: the type and degree of the response tobe achieved; the activity of the specific composition employed; the age,body weight, general health, sex and diet of the patient; the durationof the treatment; drugs used in combination or coincidental with themethod of the present disclosure; and like factors well known in themedical arts.

In some embodiments, an amount of passion flower provided per doseranges from between about 125 mg to about 500 mg. In other embodiments,an amount of passion flower provided per dose ranges from between about175 mg to about 400 mg. In yet other embodiments, an amount of passionflower provided per dose ranges from between about 200 mg to about 300mg. In further embodiments, an amount of passion flower provided perdose is about 250 mg. In some embodiments, passion flower isadministered in an amount ranging from about 4 mg/kg/day to about 20mg/kg/day. In some embodiments, passion flower is administered in anamount ranging from about 6 mg/kg/day to about 12 mg/kg/day.

In some embodiments, an amount of a root extract from a Valerian speciesprovided per dose ranges from between about 500 mg to about 1500 mg. Inother embodiments, an amount of a root extract from a Valerian speciesprovided per dose ranges from between about 750 mg to about 1250 mg. Inyet other embodiments, an amount of a root extract from a Valerianspecies provided per dose ranges from between about 900 mg to about 1100mg. In further embodiments, an amount of a root extract from a Valerianspecies provided per dose is about 1000 mg. In some embodiments, a rootextract from a Valerian species is administered in an amount rangingfrom about 10 mg/kg/day to about 50 mg/kg/day. In some embodiments, aroot extract from a Valerian species is administered in an amountranging from about 15 mg/kg/day to about 45 mg/kg/day.

In some embodiments, an amount of Ashwagandha provided per dose rangesfrom between about 250 mg to about 1000 mg. In other embodiments, anamount of Ashwagandha provided per dose ranges from between about 300 mgto about 700 mg. In yet other embodiments, an amount of Ashwagandhaprovided per dose ranges from between about 400 mg to about 600 mg. Infurther embodiments, an amount of Ashwagandha provided per dose is about500 mg. In some embodiments Ashwagandha is administered in an amountranging from about 7.5 mg/kg/day to about 20 mg/kg/day. In someembodiments, Ashwagandha is administered in an amount ranging from about10 mg/kg/day to about 30 mg/kg/day.

In some embodiments, an amount of spikenard provided per dose rangesfrom between about 150 mg to about 600 mg. In other embodiments, anamount of spikenard provided per dose ranges from between about 200 mgto about 500 mg. In yet other embodiments, an amount of spikenardprovided per dose ranges from between about 250 mg to about 350 mg. Infurther embodiments, an amount of spikenard provided per dose is about350 mg. In some embodiments spikenard is administered in an amountranging from about 4.5 mg/kg/day to about 24 mg/kg/day. In someembodiments, spikenard is administered in an amount ranging from about 6mg/kg/day to about 15 mg/kg/day.

In some embodiments, an amount of cannabidiol provided per dose rangesfrom between about 100 mg to about 400mg. In other embodiments, anamount of cannabidiol provided per dose ranges from between about 150 mgto about 250 mg. In yet other embodiments, an amount of cannabidiolprovided per dose ranges from between about 175 mg to about 225 mg. Infurther embodiments, an amount of cannabidiol provided per dose is about200 mg. In some embodiments cannabidiol is administered in an amountranging from about 3 mg/kg/day to about 16 mg/kg/day. In someembodiments, cannabidiol is administered in an amount ranging from about4 mg/kg/day to about 12 mg/kg/day.

In some embodiments, the natural product composition is administeredonce per day. In other embodiments, the natural product composition isadministered twice per day. In other embodiments, the natural productcomposition is administered at least three times per day. In someembodiments, the natural product composition may be administered every12 hours. In other embodiments, the natural product composition may beadministered every 8 hours. In yet other embodiments, the naturalproduct composition may be administered every 4 hours. In even furtherembodiments, the natural product composition may be administered on anas-needed basis, but where the number of dosages in a 24-hour perioddoes not exceed a predetermined number of doses or a predeterminedamount of each active component. In some embodiments, the naturalproduct composition is administered with food. In other embodiments, thenatural product composition is administered while in a fasted state.

Any of the natural product compositions described herein can be providedin a unit dosage form. A unit dosage is a total amount of all of theactive components within the natural product compositions, which maydelivered alone or in combination with other components, and which is tobe administered to a subject at or about one time point. Othercomponents which can be included with a unit dosage include, but are notlimited, food carriers (e.g. gelatin or gelatin substitutes), dairyproducts, oils, beverages, such as denoted herein. A unit dosage of anatural product composition may comprise about 1000, 1250, 1500, 1750,2000, 2500, 3000, 3250, 3500, 3750, 4000, 4250, 4500, 4750, 5000, 5250,5500, 5750 or more milligrams (mg) of combined active components. A unitdosage of a natural product composition may comprise at least about1000, 1250, 1500, 1750, 2000, 2500, 3000, 3250, 3500, 3750, 4000, 4250,4500, 4750, 5000, 5250, 5500, 5750 or more milligrams (mg) of combinedactive components. A unit dosage of a natural product composition maycomprise at most about 1000, 1250, 1500, 1750, 2000, 2500, 3000, 3250,3500, 3750, 4000, 4250, 4500, 4750, 5000, 5250, 5500, 5750 or moremilligrams (mg) of combined active components. A unit dosage can be anhourly dosage. A unit dosage can be a daily dosage. A unit dosage canprovide about 1/24, 1/12, ⅛, ⅙, ¼, ⅓, ½, or all of a daily dosage of oneor more natural product compositions for a subject in need thereof. Asnoted herein, a unit dosage can take the form of a tablet, gel, liquid,food product, food bar, container of liquid of defined volume, or otherforms described herein, packaged for one-time consumption oradministration.

Methods of Treatment

According to the methods of the disclosure, the compositions may beadministered to a subject to treat (i) ADD/ADHD and related disorders,including amelioration of ADD/ADHD and related symptoms; (ii) anxietyand related disorders, including amelioration of anxiety and relatedsymptoms; and (iii) depression and related disorders, includingamelioration of depression and related symptoms. Advantageously, thecompositions disclosed herein provide an over the counter and sideeffect-free treatment option for children, adolescents and adultsafflicted with ADD, ADHD, and related disorders; and anxiety anddepression.

In some embodiments, the present disclosure relates to a method for thetreatment and/or prevention of ADHD, comprising the administration of atherapeutically effective amount of a natural product component, aloneor in combination with a pharmaceutically acceptable carrier orexcipient. In some embodiments, the method comprises administering anatural product composition comprising (i) passion flower in an amountranging from between about 5% to about 17.5% by total weight of thenatural product composition; (ii) a root extract from a Valerian speciesin an amount ranging from between about 30% to about 60% by total weightof the natural product composition; (iii) Ashwagandha in an amountranging from between about 10% to about 30% by total weight of thenatural product composition; (iv) spikenard in an amount ranging frombetween about 5% to about 20% by total weight of the natural productcomposition; and (v) cannabidiol in an amount ranging from between about2% to about 20% by total weight of the natural product composition. Insome embodiments, the method comprises administering a natural productcomposition, such as denoted herein, together with a pharmaceuticallyacceptable excipient, carrier, and/or additive. In some embodiments, themethod comprises administered a natural product composition embeddedwithin a food composition or food product. In some embodiments, themethod comprises co-administering another agent for treating ADD or ADHDor for mitigating symptoms of ADD or ADHD.

In some embodiments, the present disclosure relates to a method for thetreatment and/or prevention of ADHD of predominantly impulsivity type,comprising the administration of a therapeutically effective amount of anatural product component, alone or in combination with apharmaceutically acceptable carrier or excipient. In some embodiments,the method comprising administering a natural product compositioncomprising (i) passion flower in an amount ranging from between about 5%to about 17.5% by total weight of the natural product composition; (ii)a root extract from a Valerian species in an amount ranging from betweenabout 30% to about 60% by total weight of the natural productcomposition; (iii) Ashwagandha in an amount ranging from between about10% to about 30% by total weight of the natural product composition;(iv) spikenard in an amount ranging from between about 5% to about 20%by total weight of the natural product composition; and (v) cannabidiolin an amount ranging from between about 2% to about 20% by total weightof the natural product composition. In some embodiments, the methodcomprises administering a natural product composition, such as denotedherein, together with a pharmaceutically acceptable excipient, carrier,and/or additive. In some embodiments, the method comprises administereda natural product composition embedded within a food composition or foodproduct.

In some embodiments, the present disclosure relates to a method for thetreatment and/or prevention of ADHD of predominantly inattentive type,comprising the administration of a therapeutically effective amount of anatural product component, alone or in combination with apharmaceutically acceptable carrier or excipient. In some embodiments,the method comprising administering a natural product compositioncomprising (i) passion flower in an amount ranging from between about 5%to about 17.5% by total weight of the natural product composition; (ii)a root extract from a Valerian species in an amount ranging from betweenabout 30% to about 60% by total weight of the natural productcomposition; (iii) Ashwagandha in an amount ranging from between about10% to about 30% by total weight of the natural product composition;(iv) spikenard in an amount ranging from between about 5% to about 20%by total weight of the natural product composition; and (v) cannabidiolin an amount ranging from between about 2% to about 20% by total weightof the natural product composition. In some embodiments, the methodcomprises administering a natural product composition, such as denotedherein, together with a pharmaceutically acceptable excipient, carrier,and/or additive. In some embodiments, the method comprises administereda natural product composition embedded within a food composition or foodproduct.

In some embodiments, the present disclosure relates to a method for thetreatment and/or prevention of ADHD of predominantlyhyperactive-impulsive type, comprising the administration of atherapeutically effective amount of a natural product component, aloneor in combination with a pharmaceutically acceptable carrier orexcipient. In some embodiments, the method comprising administering anatural product composition comprising (i) passion flower in an amountranging from between about 5% to about 17.5% by total weight of thenatural product composition; (ii) a root extract from a Valerian speciesin an amount ranging from between about 30% to about 60% by total weightof the natural product composition; (iii) Ashwagandha in an amountranging from between about 10% to about 30% by total weight of thenatural product composition; (iv) spikenard in an amount ranging frombetween about 5% to about 20% by total weight of the natural productcomposition; and (v) cannabidiol in an amount ranging from between about2% to about 20% by total weight of the natural product composition. Insome embodiments, the method comprises administering a natural productcomposition, such as denoted herein, together with a pharmaceuticallyacceptable excipient, carrier, and/or additive. In some embodiments, themethod comprises administered a natural product composition embeddedwithin a food composition or food product.

In some embodiments, the present disclosure relates to a method for thetreatment and/or prevention of anxiety, comprising the administration ofa therapeutically effective amount of a natural product component, aloneor in combination with a pharmaceutically acceptable carrier orexcipient. In some embodiments, the method comprises administering anatural product composition comprising (i) passion flower in an amountranging from between about 5% to about 17.5% by total weight of thenatural product composition; (ii) a root extract from a Valerian speciesin an amount ranging from between about 30% to about 60% by total weightof the natural product composition; (iii) Ashwagandha in an amountranging from between about 10% to about 30% by total weight of thenatural product composition; (iv) spikenard in an amount ranging frombetween about 5% to about 20% by total weight of the natural productcomposition; and (v) cannabidiol in an amount ranging from between about2% to about 20% by total weight of the natural product composition. Insome embodiments, the method comprises administering a natural productcomposition, such as denoted herein, together with a pharmaceuticallyacceptable excipient, carrier, and/or additive. In some embodiments, themethod comprises administered a natural product composition embeddedwithin a food composition or food product.

In some embodiments, the present disclosure relates to a method for thetreatment and/or prevention of depression, comprising the administrationof a therapeutically effective amount of a natural product component,alone or in combination with a pharmaceutically acceptable carrier orexcipient. In some embodiments, the method comprises administering anatural product composition comprising (i) passion flower in an amountranging from between about 5% to about 17.5% by total weight of thenatural product composition; (ii) a root extract from a Valerian speciesin an amount ranging from between about 30% to about 60% by total weightof the natural product composition; (iii) Ashwagandha in an amountranging from between about 10% to about 30% by total weight of thenatural product composition; (iv) spikenard in an amount ranging frombetween about 5% to about 20% by total weight of the natural productcomposition; and (v) cannabidiol in an amount ranging from between about2% to about 20% by total weight of the natural product composition. Insome embodiments, the method comprises administering a natural productcomposition, such as denoted herein, together with a pharmaceuticallyacceptable excipient, carrier, and/or additive. In some embodiments, themethod comprises administered a natural product composition embeddedwithin a food composition or food product.

In some embodiments, the natural product compositions disclosed hereinmay be administered in a combination therapy, i.e., eithersimultaneously in single or separate dosage forms or in separate dosageforms within hours or days of each other. Examples of compounds/drugsused in such combination therapies for the treatment of ADD or ADHDinclude without limitation, Dextroamphetamine Sulf-Saccharate,Dextroamphetamine Sulfate, Dexmethylphenidate HCL, Methylphenidate HCL,Methylphenidate, Amphetamine Sulfate, Lisdexamfetamine Dimesylate,Clonidine HCL, Clonidine, Guanfacine HCL, Atomoxetine HCL, GuanfacineHCL, Nortriptyline HCL, Desipramine HCL, Imipramine HCL, and BupropionHCL.

In some embodiments, the natural product compositions disclosed hereinmay be administered in a combination therapy, i.e., eithersimultaneously in single or separate dosage forms or in separate dosageforms within hours or days of each other. Examples of compounds/drugsused in such combination therapies for the treatment of anxiety includewithout limitation, Citalopram, Duloxetine, Escitalopram, Fluoxetine,Fluvoxamine, Paroxetine, Sertraline, Trazodone, Venlafaxine,Clomipramine, Desipramine, Doxepin, Imipramine, Isocarboxazid,Phenelzine, Selegiline, Tranylcypromine, Alprazolam, Chlordiazepoxide,Clonazepam, Diazepam, Lorazepam, Oxazepam, Divalproex, Gabapentin,Pregabalin, Atenolol, Nadolol, Propranolol, Molindone, Olanzapine,Quetiapine, and Risperidone. In some embodiments, the natural productcompositions disclosed herein may be administered in a combinationtherapy, i.e., either simultaneously in single or separate dosage formsor in separate dosage forms within hours or days of each other. Examplesof compounds/drugs used in such combination therapies for the treatmentof depression include without limitation, selective serotonin reuptakeinhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors(SNRIs), tricyclic antidepressants (TCAs), tetracyclic antidepressants,dopamine reuptake blockers, 5-HT1A receptor antagonists, 5-HT2 receptorantagonists, 5-HT3 receptor antagonists, monoamine oxidase inhibitors(MAOIs), and noradrenergic antagonists. Specific examples ofanti-depressants include, but are not limited to, desvenlafaxine,duloxetine, levomilnacipran, venlafaxine, amitriptyline, amoxapine,clomipramine, desipramine, doxepin, imipramine, nortriptyline,protriptyline, trimipramine, bupropion, maprotiline, vilazodone,nefazodone, trazodone, vortioxetine, isocarboxazid, phenelzine,selegiline, tranylcypromine, and mirtazapine.

Stability

In some embodiments, the individual components of the natural productcompositions of the present disclosure do not degrade to an unacceptableextent such that the final product has a shelf-life of at least about 2years. As previously mentioned, this means that the active componentswithin the dosage form remains within 90-110% of its initial amount inthe dosage form during the desired (e.g., labeled) shelf-life of thedosage form (e.g., a minimum of 2 years after the date of manufacture ofthe dosage form). In some embodiments, the natural product compositionsdescribed herein can have a shelf half-life of at least about 1, 2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22,23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80,85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210,240, 270, 300, 330, or 360 days. In some cases, the natural productcompositions described herein can have a shelf half-life of at leastabout 1, 2, 3, 4, or 5 years.

Additional Embodiments

A natural product composition comprising (i) passion flower in an amountranging from between about 5% to about 17.5% by total weight of thenatural product composition; (ii) a root extract from a Valerian speciesin an amount ranging from between about 30% to about 60% by total weightof the natural product composition; (iii) Ashwagandha in an amountranging from between about 10% to about 30% by total weight of thenatural product composition; (iv) spikenard in an amount ranging frombetween about 5% to about 20% by total weight of the natural productcomposition; and (v) cannabidiol in an amount ranging from between about2% to about 20% by total weight of the natural product composition.

A formulation comprising a natural product composition comprising (i)passion flower in an amount ranging from between about 5% to about 17.5%by total weight of the natural product composition; (ii) a root extractfrom a Valerian species in an amount ranging from between about 30% toabout 60% by total weight of the natural product composition; (iii)Ashwagandha in an amount ranging from between about 10% to about 30% bytotal weight of the natural product composition; (iv) spikenard in anamount ranging from between about 5% to about 20% by total weight of thenatural product composition; and (v) cannabidiol in an amount rangingfrom between about 2% to about 20% by total weight of the naturalproduct composition; and a pharmaceutically acceptable excipient orcarrier.

A method of treating ADHD comprising administering a therapeuticallyeffective dose of a formulation to a patient in need to treatmentthereof, the formulation comprising a natural product compositioncomprising (i) passion flower in an amount ranging from between about 5%to about 17.5% by total weight of the natural product composition; (ii)a root extract from a Valerian species in an amount ranging from betweenabout 30% to about 60% by total weight of the natural productcomposition; (iii) Ashwagandha in an amount ranging from between about10% to about 30% by total weight of the natural product composition;(iv) spikenard in an amount ranging from between about 5% to about 20%by total weight of the natural product composition; and (v) cannabidiolin an amount ranging from between about 2% to about 20% by total weightof the natural product composition; and a pharmaceutically acceptableexcipient or carrier.

A method of mitigating the symptoms of ADHD comprising administering atherapeutically effective dose of a formulation to a patient in needthereof, the formulation comprising a natural product compositioncomprising (i) passion flower in an amount ranging from between about 5%to about 17.5% by total weight of the natural product composition; (ii)a root extract from a Valerian species in an amount ranging from betweenabout 30% to about 60% by total weight of the natural productcomposition; (iii) Ashwagandha in an amount ranging from between about10% to about 30% by total weight of the natural product composition;(iv) spikenard in an amount ranging from between about 5% to about 20%by total weight of the natural product composition; and (v) cannabidiolin an amount ranging from between about 2% to about 20% by total weightof the natural product composition; and a pharmaceutically acceptableexcipient or carrier.

A method of delaying the onset of symptoms associated with ADHDcomprising administering a therapeutically effective dose of aformulation to a patient in need thereof, the formulation comprising anatural product composition comprising (i) passion flower in an amountranging from between about 5% to about 17.5% by total weight of thenatural product composition; (ii) a root extract from a Valerian speciesin an amount ranging from between about 30% to about 60% by total weightof the natural product composition; (iii) Ashwagandha in an amountranging from between about 10% to about 30% by total weight of thenatural product composition; (iv) spikenard in an amount ranging frombetween about 5% to about 20% by total weight of the natural productcomposition; and (v) cannabidiol in an amount ranging from between about2% to about 20% by total weight of the natural product composition; anda pharmaceutically acceptable excipient or carrier.

A composition comprising: (a) a natural product composition comprising(i) passion flower in an amount ranging from between about 5% to about17.5% by total weight of the natural product composition; (ii) a rootextract from a Valerian species in an amount ranging from between about30% to about 60% by total weight of the natural product composition;(iii) Ashwagandha in an amount ranging from between about 10% to about30% by total weight of the natural product composition; (iv) spikenardin an amount ranging from between about 5% to about 20% by total weightof the natural product composition; and (v) cannabidiol in an amountranging from between about 2% to about 20% by total weight of thenatural product composition; (b) and another active pharmaceuticalingredient, for the treatment of ADHD.

A food product comprising a natural product composition comprising (i)passion flower in an amount ranging from between about 5% to about 17.5%by total weight of the natural product composition; (ii) a root extractfrom a Valerian species in an amount ranging from between about 30% toabout 60% by total weight of the natural product composition; (iii)Ashwagandha in an amount ranging from between about 10% to about 30% bytotal weight of the natural product composition; (iv) spikenard in anamount ranging from between about 5% to about 20% by total weight of thenatural product composition; and (v) cannabidiol in an amount rangingfrom between about 2% to about 20% by total weight of the naturalproduct composition. In some embodiments, the natural productcomposition of claim 1 is admixed with a gelatin-based foodstuff.

A method of treating anxiety comprising administering a therapeuticallyeffective dose of a formulation to a patient in need of treatmentthereof, the formulation comprising a natural product compositioncomprising (i) passion flower in an amount ranging from between about 5%to about 17.5% by total weight of the natural product composition; (ii)a root extract from a Valerian species in an amount ranging from betweenabout 30% to about 60% by total weight of the natural productcomposition; (iii) Ashwagandha in an amount ranging from between about10% to about 30% by total weight of the natural product composition;(iv) spikenard in an amount ranging from between about 5% to about 20%by total weight of the natural product composition; and (v) cannabidiolin an amount ranging from between about 2% to about 20% by total weightof the natural product composition; and a pharmaceutically acceptableexcipient or carrier.

A method of mitigating the symptoms of anxiety comprising administeringa therapeutically effective dose of a formulation to a patient in needthereof, the formulation comprising a natural product compositioncomprising (i) passion flower in an amount ranging from between about 5%to about 17.5% by total weight of the natural product composition; (ii)a root extract from a Valerian species in an amount ranging from betweenabout 30% to about 60% by total weight of the natural productcomposition; (iii) Ashwagandha in an amount ranging from between about10% to about 30% by total weight of the natural product composition;(iv) spikenard in an amount ranging from between about 5% to about 20%by total weight of the natural product composition; and (v) cannabidiolin an amount ranging from between about 2% to about 20% by total weightof the natural product composition; and a pharmaceutically acceptableexcipient or carrier.

A method of delaying the onset of symptoms associated with anxietycomprising administering a therapeutically effective dose of a to apatient in need thereof, the formulation comprising a natural productcomposition comprising (i) passion flower in an amount ranging frombetween about 5% to about 17.5% by total weight of the natural productcomposition; (ii) a root extract from a Valerian species in an amountranging from between about 30% to about 60% by total weight of thenatural product composition; (iii) Ashwagandha in an amount ranging frombetween about 10% to about 30% by total weight of the natural productcomposition; (iv) spikenard in an amount ranging from between about 5%to about 20% by total weight of the natural product composition; and (v)cannabidiol in an amount ranging from between about 2% to about 20% bytotal weight of the natural product composition; and a pharmaceuticallyacceptable excipient or carrier.

A method of treating depression comprising administering atherapeutically effective dose of a formulation a patient in needthereof, the formulation comprising a natural product compositioncomprising (i) passion flower in an amount ranging from between about 5%to about 17.5% by total weight of the natural product composition; (ii)a root extract from a Valerian species in an amount ranging from betweenabout 30% to about 60% by total weight of the natural productcomposition; (iii) Ashwagandha in an amount ranging from between about10% to about 30% by total weight of the natural product composition;(iv) spikenard in an amount ranging from between about 5% to about 20%by total weight of the natural product composition; and (v) cannabidiolin an amount ranging from between about 2% to about 20% by total weightof the natural product composition; and a pharmaceutically acceptableexcipient or carrier.

A method of mitigating the symptoms of depression comprisingadministering a therapeutically effective dose of a formulation to apatient in need thereof, the formulation comprising a natural productcomposition comprising (i) passion flower in an amount ranging frombetween about 5% to about 17.5% by total weight of the natural productcomposition; (ii) a root extract from a Valerian species in an amountranging from between about 30% to about 60% by total weight of thenatural product composition; (iii) Ashwagandha in an amount ranging frombetween about 10% to about 30% by total weight of the natural productcomposition; (iv) spikenard in an amount ranging from between about 5%to about 20% by total weight of the natural product composition; and (v)cannabidiol in an amount ranging from between about 2% to about 20% bytotal weight of the natural product composition; and a pharmaceuticallyacceptable excipient or carrier.

A method of delaying the onset of symptoms associated with depressioncomprising administering a therapeutically effective dose of aformulation to a patient in need thereof, the formulation comprising anatural product composition comprising (i) passion flower in an amountranging from between about 5% to about 17.5% by total weight of thenatural product composition; (ii) a root extract from a Valerian speciesin an amount ranging from between about 30% to about 60% by total weightof the natural product composition; (iii) Ashwagandha in an amountranging from between about 10% to about 30% by total weight of thenatural product composition; (iv) spikenard in an amount ranging frombetween about 5% to about 20% by total weight of the natural productcomposition; and (v) cannabidiol in an amount ranging from between about2% to about 20% by total weight of the natural product composition; anda pharmaceutically acceptable excipient or carrier.

A composition comprising a natural product mixture and another activepharmaceutical ingredient for the treatment of anxiety, the naturalproduct mixture comprising (i) passion flower in an amount ranging frombetween about 5% to about 17.5% by total weight of the natural productcomposition; (ii) a root extract from a Valerian species in an amountranging from between about 30% to about 60% by total weight of thenatural product composition; (iii) Ashwagandha in an amount ranging frombetween about 10% to about 30% by total weight of the natural productcomposition; (iv) spikenard in an amount ranging from between about 5%to about 20% by total weight of the natural product composition; and (v)cannabidiol in an amount ranging from between about 2% to about 20% bytotal weight of the natural product composition.

A composition comprising the natural product mixture and another activepharmaceutical ingredient for the treatment of depression, the naturalproduct mixture comprising (i) passion flower in an amount ranging frombetween about 5% to about 17.5% by total weight of the natural productcomposition; (ii) a root extract from a Valerian species in an amountranging from between about 30% to about 60% by total weight of thenatural product composition; (iii) Ashwagandha in an amount ranging frombetween about 10% to about 30% by total weight of the natural productcomposition; (iv) spikenard in an amount ranging from between about 5%to about 20% by total weight of the natural product composition; and (v)cannabidiol in an amount ranging from between about 2% to about 20% bytotal weight of the natural product composition.

A natural product composition comprising cannabidiol and a hemp oil. Insome embodiments, the natural product comprising further compries atleast one of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard. In some embodiments, the natural productcomprising further compries at least two of passion flower, a rootextract from a Valerian species, Ashwagandha, and spikenard. In someembodiments, the natural product comprising further compries at leastthree of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard. In some embodiments, the natural productcomprising further compries passion flower, a root extract from aValerian species, Ashwagandha, and spikenard.

A natural product consisting essentially of comprising cannabidiol and ahemp oil.

A formulation comprising a natural product composition and apharmaceutically acceptable excipient or carrier, wherein the naturalproduct comprises cannabidiol and a hemp oil. In some embodiments, thenatural product comprising further compries at least one of passionflower, a root extract from a Valerian species, Ashwagandha, andspikenard. In some embodiments, the natural product comprising furthercompries at least two of passion flower, a root extract from a Valerianspecies, Ashwagandha, and spikenard. In some embodiments, the naturalproduct comprising further compries at least three of passion flower, aroot extract from a Valerian species, Ashwagandha, and spikenard. Insome embodiments, the natural product comprising further compriespassion flower, a root extract from a Valerian species, Ashwagandha, andspikenard.

A method of treating ADHD comprising administering a therapeuticallyeffective dose of a formulation to a patient in need thereof, theformulation comprising cannabidiol and a hemp oil. In some embodiments,the natural product formulation further comprises at least one ofpassion flower, a root extract from a Valerian species, Ashwagandha, andspikenard. In some embodiments, the natural product formulation furthercomprises at least two of passion flower, a root extract from a Valerianspecies, Ashwagandha, and spikenard. In some embodiments, the naturalproduct formulation further comprises at least three of passion flower,a root extract from a Valerian species, Ashwagandha, and spikenard. Insome embodiments, the natural product formulation further comprisespassion flower, a root extract from a Valerian species, Ashwagandha, andspikenard.

A method of mitigating the symptoms of ADHD comprising administering atherapeutically effective dose of a formulation to a patient in needthereof, the formulation comprising cannabidiol and a hemp oil. In someembodiments, the natural product formulation further comprises at leastone of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard. In some embodiments, the natural productformulation further comprises at least two of passion flower, a rootextract from a Valerian species, Ashwagandha, and spikenard. In someembodiments, the natural product formulation further comprises at leastthree of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard. In some embodiments, the natural productformulation further comprises passion flower, a root extract from aValerian species, Ashwagandha, and spikenard.

A method of delaying the onset of symptoms associated with ADHDcomprising administering a therapeutically effective dose of aformulation to a patient in need thereof, the formulation comprisingcannabidiol and a hemp oil. In some embodiments, the natural productformulation further comprises at least one of passion flower, a rootextract from a Valerian species, Ashwagandha, and spikenard. In someembodiments, the natural product formulation further comprises at leasttwo of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard. In some embodiments, the natural productformulation further comprises at least three of passion flower, a rootextract from a Valerian species, Ashwagandha, and spikenard. In someembodiments, the natural product formulation further comprises passionflower, a root extract from a Valerian species, Ashwagandha, andspikenard.

A composition comprising a natural product composition and at least oneadditional active pharmaceutical ingredient for the treatment of ADHD,the natural product composition comprising a cannabidiol and a hemp oil.In some embodiments, the natural product composition further comprisesat least one of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard. In some embodiments, the natural productcomposition further comprises at least two of passion flower, a rootextract from a Valerian species, Ashwagandha, and spikenard. In someembodiments, the natural product composition further comprises at leastthree of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard. In some embodiments, the natural productcomposition further comprises passion flower, a root extract from aValerian species, Ashwagandha, and spikenard.

A food product comprising a natural product composition comprising acannabidiol and a hemp oil. In some embodiments, the natural productcomposition further comprises at least one of passion flower, a rootextract from a Valerian species, Ashwagandha, and spikenard. In someembodiments, the natural product composition further comprises at leasttwo of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard. In some embodiments, the natural productcomposition further comprises at least three of passion flower, a rootextract from a Valerian species, Ashwagandha, and spikenard. In someembodiments, the natural product composition further comprises passionflower, a root extract from a Valerian species, Ashwagandha, andspikenard. In some embodiments, the natural product composition of isadmixed with a gelatin-based foodstuff.

A method of treating anxiety comprising administering a therapeuticallyeffective dose of a formulation to a patient in need thereof, theformulation comprising cannabidiol and a hemp oil. In some embodiments,the natural product formulation further comprises at least one ofpassion flower, a root extract from a Valerian species, Ashwagandha, andspikenard. In some embodiments, the natural product formulation furthercomprises at least two of passion flower, a root extract from a Valerianspecies, Ashwagandha, and spikenard. In some embodiments, the naturalproduct formulation further comprises at least three of passion flower,a root extract from a Valerian species, Ashwagandha, and spikenard. Insome embodiments, the natural product formulation further comprisespassion flower, a root extract from a Valerian species, Ashwagandha, andspikenard.

A method of mitigating the symptoms of anxiety comprising administeringa therapeutically effective dose of a formulation oto a patient in needthereof, the formulation comprising cannabidiol and a hemp oil. In someembodiments, the natural product formulation further comprises at leastone of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard. In some embodiments, the natural productformulation further comprises at least two of passion flower, a rootextract from a Valerian species, Ashwagandha, and spikenard. In someembodiments, the natural product formulation further comprises at leastthree of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard. In some embodiments, the natural productformulation further comprises passion flower, a root extract from aValerian species, Ashwagandha, and spikenard.

A method of delaying the onset of symptoms associated with anxietycomprising administering a therapeutically effective dose of aformulation to a patient in need thereof, the formulation comprisingcannabidiol and a hemp oil. In some embodiments, the natural productformulation further comprises at least one of passion flower, a rootextract from a Valerian species, Ashwagandha, and spikenard. In someembodiments, the natural product formulation further comprises at leasttwo of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard. In some embodiments, the natural productformulation further comprises at least three of passion flower, a rootextract from a Valerian species, Ashwagandha, and spikenard. In someembodiments, the natural product formulation further comprises passionflower, a root extract from a Valerian species, Ashwagandha, andspikenard.

A method of treating depression comprising administering atherapeutically effective dose of a formulation to a patient in needthereof, the formulation comprising cannabidiol and a hemp oil. In someembodiments, the natural product formulation further comprises at leastone of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard. In some embodiments, the natural productformulation further comprises at least two of passion flower, a rootextract from a Valerian species, Ashwagandha, and spikenard. In someembodiments, the natural product formulation further comprises at leastthree of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard. In some embodiments, the natural productformulation further comprises passion flower, a root extract from aValerian species, Ashwagandha, and spikenard.

A method of mitigating the symptoms of depression comprisingadministering a therapeutically effective dose of a to a patient in needthereof, the formulation comprising cannabidiol and a hemp oil. In someembodiments, the natural product formulation further comprises at leastone of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard. In some embodiments, the natural productformulation further comprises at least two of passion flower, a rootextract from a Valerian species, Ashwagandha, and spikenard. In someembodiments, the natural product formulation further comprises at leastthree of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard. In some embodiments, the natural productformulation further comprises passion flower, a root extract from aValerian species, Ashwagandha, and spikenard.

A method of delaying the onset of symptoms associated with depressioncomprising administering a therapeutically effective dose of aformulation to a patient in need thereof, the formulation comprisingcannabidiol and a hemp oil. In some embodiments, the natural productformulation further comprises at least one of passion flower, a rootextract from a Valerian species, Ashwagandha, and spikenard. In someembodiments, the natural product formulation further comprises at leasttwo of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard. In some embodiments, the natural productformulation further comprises at least three of passion flower, a rootextract from a Valerian species, Ashwagandha, and spikenard. In someembodiments, the natural product formulation further comprises passionflower, a root extract from a Valerian species, Ashwagandha, andspikenard.

A composition comprising a natural product composition and at least oneother active pharmaceutical ingredient for the treatment of anxiety, thenatural product composition comprising a cannabidiol and a hemp oil. Insome embodiments, the natural product composition further comprises atleast one of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard. In some embodiments, the natural productcomposition further comprises at least two of passion flower, a rootextract from a Valerian species, Ashwagandha, and spikenard. In someembodiments, the natural product composition further comprises at leastthree of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard. In some embodiments, the natural productcomposition further comprises passion flower, a root extract from aValerian species, Ashwagandha, and spikenard.

A composition comprising a natural product composition and at least oneother active pharmaceutical ingredient for the treatment of depression,the natural product composition comprising a cannabidiol and a hemp oil.In some embodiments, the natural product composition further comprisesat least one of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard. In some embodiments, the natural productcomposition further comprises at least two of passion flower, a rootextract from a Valerian species, Ashwagandha, and spikenard. In someembodiments, the natural product composition further comprises at leastthree of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard. In some embodiments, the natural productcomposition further comprises passion flower, a root extract from aValerian species, Ashwagandha, and spikenard.

EXAMPLE 1 The Following Table Provides an Exemplary Embodiment of aNatural Product Composition of the Present Disclosure.

Percent by total weight of the Active Component natural productcomposition Cannabidiol  9% Spikenard 13% root extract from a Valerianspecies 44% passion flower extract 11% Ashwagandha 22%

EXAMPLE 2 The Following Table Provides an Exemplary Embodiment of aSingle Dose of a Natural Product Composition.

Amount in a suitable Active Component dosage unit (mg) Cannabidiol 200mg Spikenard 300 mg root extract from a Valerian species 1000 mg passion flower extract 250 mg Ashwagandha 500 mg

EXAMPLE 3 The Table Below Sets Forth Exemplary Dosage Amounts for aPediatric Patient.

Active Component Dosage Cannabidiol 6 mg/kg/day Spikenard 9 mg/kg/dayroot extract from a Valerian species 20 mg/kg/day passion flower extract7.5 mg/kg/day Ashwagandha 15 mg/kg/day

EXAMPLE 4 The Table Below Sets Forth Exemplary Dosage Amounts for anAdult Patient.

Active Component Dosage Cannabidiol  8 mg/kg/day Spikenard 12 mg/kg/dayroot extract from a Valerian species 30 mg/kg/day passion flower extract10 mg/kg/day Ashwagandha 20 mg/kg/day

1. A natural product composition comprising (i) a therapeuticallyeffective amount of a cannabidiol; (ii) a medium chain triglyceride; and(iii) and a therapeutically effective amount of at least one additionalactive component.
 2. The natural product composition of claim 1, whereinthe at least one additional active component is an active pharmaceuticalingredient.
 3. The natural product composition of claim 1, wherein theat least one additional active component is selected from the groupconsisting of passion flower, a root extract from a valerian species,ashwagandha, and spikenard.
 4. The natural product composition of claim3, wherein the at least one additional active component comprises atleast two of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard.
 5. The natural product composition of claim3, wherein the at least one additional active component comprises atleast three of passion flower, a root extract from a Valerian species,Ashwagandha, and spikenard.
 6. The natural product of claim 1, whereinthe cannabidiol comprises 2-[3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol or a salt, or asolvate thereof.
 7. The natural product of claim 1, wherein thecannabidiol comprises a metaboloite of2-[3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediolor a salt, or a solvate thereof.
 8. The natural product of claim 1,wherein the cannabidiol comprises a metabolic precursor of2-[3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediolor a salt, or a solvate thereof.
 9. The natural product claim 1, whereinthe cannabidiol is present in the natural product composition in anamount ranging from between about 2% to about 20% by total weight of thenatural product composition.
 10. The natural product claim 1, whereinthe cannabidiol is present in the natural product composition in anamount ranging from between about 4% to about 15% by total weight of thenatural product composition.
 11. The natural product claim 1, whereinthe cannabidiol is present in the natural product composition in anamount ranging from between about 6% to about 11% by total weight of thenatural product composition.
 12. The natural product composition ofclaim 1, wherein the natural product composition comprises hemp oil andwherein the cannabidiol is at least partially present in the hemp oil.13. A natural product composition comprising (i) a cannabidiol, and (ii)and at least two additives selected from the group consisting of acompound derived or extracted from passion flower, a compound derived orextracted from valerian or valerian root, a compound derived orextracted from ashwagandha, and a compound derived or extracted fromspikenard.
 14. The natural product composition of claim 13, wherein thenatural product composition comprises hemp oil and wherein thecannabidiol is at least partially present in the hemp oil.
 15. A naturalproduct composition comprising (i) hemp oil, and (ii) and at least twoadditives selected from the group consisting of passion flower, a rootextract from a Valerian species, Ashwagandha, and spikenard.